737P - Phase I/II trial of lenvatinib (E7080), a multi-targeted tyrosine kinase inhibitor, in patients (pts) with advanced hepatocellular carcinoma (HCC)

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Drug Development
Hepatobiliary Cancers
Presenter Kenji Ikeda
Authors K. Ikeda1, H. Kumada2, M. Kudo3, S. Kawazoe4, Y. Osaki5, M. Ikeda6, T. Okusaka7, T. Suzuki8, J.P. O'Brien9, K. Okita10
  • 1Department Of Hepatology, Toranomon Hospital, Tokyo/JP
  • 2Department Of Hepatology, Toranomon Hospital Kajigaya, Kanagawa/JP
  • 3Department Of Gastroenterology And Hepatology, Kinki University School of Medicine, Osaka/JP
  • 4Department Of Internal Medicine, Saga prefectural Hospital Koseikan, Saga/JP
  • 5Department Of Gastroenterology And Hepatology, Osaka Red Cross Hospital, Osaka/JP
  • 6Division Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital East, Chiba/JP
  • 7Division Of Hepatobiliary And Pancreatic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 8Oncology Clinical Development, Eisai, Tokyo/JP
  • 9Oncology, Eisai Inc., 07677 - Woodcliff Lake/US
  • 10Department Of Gastroenterology And Hepatology, Shimonoseki Kohsei Hospital, Yamaguchi/JP

Abstract

Background

Lenvatinib is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFR�. The inherent vascularity of HCC makes it a target for VEGF inhibitors and other molecular mediators of angiogenesis like FGFR and PDGFR. The current study established a MTD of lenvatinib for HCC patients with Child-Pugh A of 12 mg qd. The current presentation is a report on the efficacy and safety of lenvatinib.

Methods

Between July 9, 2010 and June 22, 2011, 46 pts with advanced HCC and Child-Pugh A status were enrolled in Japan (n = 43) and Korea (n = 3). Pts may have received up to one prior treatment regimen including sorafenib. Pts were treated with a starting dose of lenvatinib 12 mg once daily in 28 day cycles until disease progression or development of unmanageable toxicities. Response was assessed by RECIST 1.1 (modified to evaluate viable lesions) by independent radiologist review (IRR).

Results

46 pts were enrolled (med age: 67; M: 72%) and were evaluable for response. 76% of pts required dose adjustments for management of toxicity. The most common adverse events were hypertension 76% (Gr3: 54%), palmar-plantar erythrodysaesthesia syndrome 65% (Gr3: 9%), anorexia 59% (Gr3: 2.2%), proteinuria 54% (Gr3: 17%), fatigue 54% (Gr3: 0%), and thrombocytopenia 52% (Gr3: 33%). A higher level of toxicity was observed in pts weighing < 60 kg compared to pts ≥ 60 kg correlating with differences in drug exposure. ORR based on IRR is (PR = 32.6%, SD = 45.7%). Median Time to progression (TTP) is 7.49 mo (95% CI: 5.45 - 9.43)(based on minimum 6 mo. f/u, with 56.5% progression events) based on IRR. Median overall survival (OS) is 13.9 mo (95% CI: 11.8 -) (based on minimum 8 mo. f/u, with 46% death events). OS data has not yet matured and will be reported in the future.

Conclusions

In this Phase I/II study, lenvatinib administered to patients with advanced HCC was not associated with any new toxicities associated with TKI class and was managed by dose adjustments. A weight-based starting dose (<60 Kg: 8 mg qd, vs ≥60kg: 12 mg qd) may be appropriate to minimize toxicity due to higher drug exposure in pts < 60 kg. The observed OS and TTP indicate lenvatinib has activity in patients with advanced HCC and may be a new therapeutic option.

Disclosure

K. Ikeda: K. Ikeda has served as an advisor for Eisai and has received honoraria from Eisai.

H. Kumada: H. Kumada has served as an advisor for Eisai and has received honoraria and research funding from Eisai.

M. Kudo: M. Kudo has received honoraria from Eisai.

Y. Osaki: Y. Osaki has received honoraria from Eisai.

T. Okusaka: T. Okusakia has received honoraria from Eisai.

T. Suzuki: T. Suzuki is an employee of Eisai.

J.P. O'Brien: J. O'Brien is an employee of Eisai.

K. Okita: K. Okita has served as an advisor for Eisai and has received honoraria from Eisai.

All other authors have declared no conflicts of interest.